Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y(1) and the P2Y (12) receptor and is correlated with protein expression of P2Y (12).

Purinergic Signalling
Oscar O BraunD Erlinge

Abstract

Two ADP receptors have been identified on human platelets: P2Y(1) and P2Y(12). The P2Y(12) receptor blocker clopidogrel is widely used to reduce the risks in acute coronary syndromes, but, currently, there is no P2Y(1) blocker in clinical use. Evidence for variable responses to clopidogrel has been described in several reports. The mechanistic explanation for this phenomenon is not fully understood. The aim of this study was to examine mechanisms responsible for variability of 2MeS-ADP, a stable ADP analogue, induced platelet reactivity in clopidogrel-treated patients. Platelet reactivity was assessed by flow cytometry measurements of P-selectin (CD62P) and activated GpIIb/IIIa complex (PAC-1). Residual 2MeS-ADP activation via the P2Y(12) and P2Y(1) receptors was determined by co-incubation with the selective antagonists AR-C69931 and MRS2179 in vitro. P2Y(1) and P2Y(12) receptor expression on both RNA and protein level were determined, as well as the P2Y(12) H1 or H2 haplotypes. Our data suggest that the residual platelet activation of 2MeS-ADP after clopidogrel treatment is partly due to an inadequate antagonistic effect of clopidogrel on the P2Y(12) receptor and partly due to activation of the P2Y(1) receptor, which is unaff...Continue Reading

References

Aug 8, 2001·The Journal of Cell Biology·S LindemannA S Weyrich
Aug 25, 2001·The New England Journal of Medicine·S YusufUNKNOWN Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators
Sep 25, 2002·Journal of Internal Medicine·P JäremoA Richter
Nov 27, 2002·Journal of Cardiovascular Pharmacology·Lingwei WangDavid Erlinge
Apr 12, 2003·Current Opinion in Pharmacology·Satya P KunapuliTodd M Quinton
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·L WangD Erlinge
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·B HechlerK Ravid
Aug 20, 2003·Circulation·Jacqueline SawUNKNOWN Clopidogrel for the Reduction of Events During Observation Investigators
Jul 23, 2004·Thrombosis and Haemostasis·Dirk TaubertEdgar Schömig
Oct 30, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Simon L HetheringtonNilesh J Samani

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Citations

May 23, 2009·Inhalation Toxicology·G R ThoméM R C Schetinger
Jun 2, 2009·Scandinavian Journal of Clinical and Laboratory Investigation·Øystein MeenGunnar Erikssen
Apr 6, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lívia G CastilhosDaniela B R Leal
Aug 12, 2015·Purinergic Signalling·Geoffrey Burnstock
Sep 3, 2014·Mediators of Inflammation·Joanna LeckaJean Sévigny
Aug 25, 2015·Therapeutic Advances in Drug Safety·Isobel Ford

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Methods Mentioned

BETA
flow cytometry
protein assay
PCR
electrophoresis

Software Mentioned

LightCycler
Quantity One
GraphPad Prism

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